P75

p75, in a biological context, most often refers to the p75 neurotrophin receptor (p75NTR), also known as NGFR or CD271. It is a transmembrane glycoprotein that belongs to the tumor necrosis factor receptor (TNFR) superfamily and is encoded by the NGFR gene in humans. The receptor is broadly expressed in the nervous system, including sensory and autonomic neurons, Schwann cells, and various glial cells, and its expression can be upregulated after nerve injury. It is also found in non-neural tissues and cell types used in stem cell research and oncology.

The p75 receptor has an extracellular domain with four cysteine-rich repeats, a single transmembrane segment, and a cytoplasmic tail that contains a death domain–like region. It binds neurotrophins—nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5—with relatively low affinity when acting alone. Signaling is often modulated by forming complexes with Trk receptors (TrkA, TrkB, TrkC) to influence high-affinity neurotrophin signaling, but p75 can also signal independently. Binding of proneurotrophins in complex with sortilin can promote apoptotic pathways.

Functions of p75NTR are diverse and context-dependent. It can influence neuronal survival and apoptosis, neurite outgrowth, axon guidance, and synaptic plasticity via downstream pathways such as JNK, NF-κB, and RhoA, mediated by adaptor proteins including NRIF and NRAGE. In development, p75NTR contributes to peripheral nervous system formation and injury responses. In research and medicine, CD271 is used as a marker for neural crest–derived stem cells and, in some cancers such as melanoma, to identify subpopulations with stem-like properties.

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